RAPID REVERSAL OF ALPHA-2-ADRENOCEPTOR AGONIST EFFECTS BY ATIPAMEZOLE IN HUMAN VOLUNTEERS

1 The ability of atipamezole, a specific and selective alpha-2-adrenoceptor antagonist, to reverse the pharmacological effects induced by the alpha-2-adrenoceptor agonist dexmedetomidine was studied in six healthy male volunteers. Each volunteer received in four sessions in a randomized and single-blind manner three different doses (6.7-mu-g kg-1, 27-mu-g kg-1 and 67-mu-g kg-1) of atipamezole or saline placebo as 5 min i.v. infusions preceded by a fixed i.v. dose of dexmedetomidine (0.67-mu-g kg-1). 2 Dexmedetomidine caused profound sedation, with the subjects actually falling asleep. This was effectively reversed by the two highest doses of atipamezole. 3 Dexmedetomidine reduced salivary flow on average by 70%. A rapid and full reversal of this effect was seen after the highest dose of atipamezole. 4 Hypotension induced by dexmedetomidine was also effectively antagonized by atipamezole. Bradycardia was very modest after dexmedetomidine in this study, and thus no reversal of alpha-2-adrenoceptor agonist-induced bradycardia could be demonstrated. 5 Plasma noradrenaline concentrations were reduced by 80% by dexmedetomidine. This was effectively antagonized by atipamezole, and the highest dose caused a 50% overshoot in plasma noradrenaline concentrations over the basal levels. 6 It is concluded that the effects of dexmedetomidine are effectively reversible by atipamezole. A dose ratio of 10:1 for atipamezole: dexmedetomidine was clearly insufficient for this purpose, but ratios in the range of 40:1 to 100:1 were found to be effective in the current experimental situation.